Growth hormone (GH) secretory dynamics in animals administered estradiol utilizing a chemical delivery system.
We have utilized a redox chemical delivery system (CDS) for the brain targeting of estradiol (E2) to ascertain its effects on GH secretory patterns in adult intact male rats. The E2-CDS (1.0 mg/kg) dissolved in 20% hydroxypropyl-cyclodextrin (HPCD), E2 (1.0 mg/kg) alone in 20% HPCD, or 20% HPCD was administered intravenously. GH secretory profiles, plasma steroid levels, and anterior pituitary levels of hormones were determined 1 week following steroid injection. Whereas E2 in HPCD and HPCD treatment did not alter masculine GH secretory patterns, animals administered the E2-CDS displayed disrupted GH patterns with attenuated individual pulse amplitudes and significantly elevated GH baseline levels. Moderate pituitary hyperplasia was evident only in the E2-CDS group of animals. Plasma testosterone (T) concentrations were reduced in only the E2-CDS group. T replacement reduced E2-CDS-associated pituitary hyperplasia and preserved the masculine GH secretory profiles, with only a slight reduction in individual GH peak amplitudes being observed. T replacement did not prevent the increase in pituitary and plasma levels of PRL associated with E2-CDS treatment but did block both the increase in pituitary GH content and the hyperplasia associated with prolonged E2 exposure. E2 given alone induced a significant increase in both GH and PRL in the pituitary without establishment of pituitary hyperplasia or elevated plasma PRL levels. These data indicate that E2-CDS is an effective mode of steroid administration. Changes in GH secretory dynamics, pituitary levels of GH, and degree of hyperplasia are dependent upon the chemical design of the delivery system for E2. Concomitant T therapy can prevent some of the changes in GH secretion associated with high-dose E2 exposure.
Millard
W J
WJ
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville 32610.
Romano
T M
TM
Bodor
N
N
Simpkins
J W
JW
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D003505:Cyclodextrins; D004337:Drug Carriers; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage*; D013006:Growth Hormone / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D010507:Periodicity; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000494:pharmacology; D013972:Thyrotropin / Q000378:metabolism; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D004337:Drug Carriers; D004343:Drug Implants; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D013739:Testosterone; D004958:Estradiol; D011388:Prolactin; D013972:Thyrotropin; D013006:Growth Hormone